Ceftriaxone Dosing for Typhoid Fever
For typhoid fever, administer ceftriaxone 75-80 mg/kg/day intravenously (maximum 2-4 g/day) once daily for 5-7 days in both adults and children. 1
Standard Dosing Regimen
The recommended approach is 80 mg/kg/day IV once daily for 5-7 days, which represents the most widely validated regimen across multiple studies. 1 This dosing achieves adequate plasma concentrations well above the MIC for Salmonella typhi throughout the 24-hour dosing interval, with mean trough levels of 21.7 mcg/ml maintaining therapeutic efficacy. 2
Pediatric Dosing Specifics
- Children should receive 75-80 mg/kg/day IV (maximum 2 g/day), administered either once daily or divided every 12 hours. 1, 3
- The once-daily dosing at approximately 80 mg/kg has demonstrated equivalent efficacy to traditional chloramphenicol therapy with cure rates of 79-100%. 3
- Ceftriaxone is contraindicated in hyperbilirubinemic neonates due to risk of bilirubin displacement. 1
Adult Dosing
- Adults typically receive 2-4 g IV once daily for 5-7 days. 1
- Single high-dose regimens (3-4 g daily) for 1-2 days have shown success in some studies, though 5-7 day courses remain the standard recommendation. 4
Treatment Duration Considerations
A flexible-duration approach is supported: continue therapy until defervescence plus an additional 5 days. 5 This strategy achieved:
- Mean defervescence time of 5.4 days 5
- Zero relapses compared to 13% relapse rate with chloramphenicol 5
- Clinical cure in 100% of patients without complications 5
The traditional 5-7 day fixed duration remains appropriate for most cases, with mean defervescence occurring at 4 days when excluding patients with complicating medical conditions. 6
Clinical Response Monitoring
Expected clinical response timeline:
- Defervescence typically occurs within 4-5 days of initiating therapy 5, 6
- Patients with persistent fever beyond 5-7 days should be evaluated for complications or treatment failure 6
- Blood cultures clear rapidly, with bacteremia resolving within the first few days of treatment 6
Important Caveats
Common pitfalls to avoid:
- Do not use inadequate duration: courses shorter than 5 days (except in specific high-dose protocols) may increase relapse risk 5
- Monitor for biliary complications: prolonged high-dose therapy can cause biliary sludging, though this is rare with standard 5-7 day courses 1
- Ensure adequate dosing in children: underdosing below 75 mg/kg/day may compromise efficacy 3
The pharmacokinetic profile in typhoid fever patients shows adequate drug exposure with once-daily dosing, with elimination half-life of 5.2 hours and 49.7% urinary excretion maintaining therapeutic levels throughout the dosing interval. 2